Inhibition of S-adenosyl-L-homocysteine hydrolase by adrenaline in isolated guinea-pig papillary muscles.
Purified S-adenosyl-L-homocysteine hydrolase from Dictyostelium discoideum or rabbit erythrocytes is inactivated when incubated with cAMP. The aim of this study was to investigate whether adrenaline, which increases cytosolic cAMP and calcium concentrations, is able to modify in situ the activity of S-adenosyl-L-homocysteine hydrolase in the heart. The enzyme was assayed in a crude extract obtained from superfused guinea-pig papillary muscles with the different tested substances. Adrenaline was found to inhibit S-adenosyl-L-homocysteine hydrolase in papillary muscles in a concentration-dependent fashion. This inhibition was associated with an increase in the concentration of S-adenosyl-L-homocysteine (326%), and a decrease of adenosine (40%). beta-Adrenoceptors are involved in the effect of adrenaline, since isoproterenol, a beta-adrenergic agonist, inhibited the enzyme, whereas the beta-adrenergic blocker, propranolol, prevented this inhibition. Participation of calcium in the inhibitory effect of adrenaline was suggested because the calcium channel blocker, verapamil, suppressed this inhibition, and high calcium in the perfusion medium inhibited the enzyme. In vitro experiments with calcium were performed in a semi-purified fraction of the enzyme, resulting in a concentration-dependent inhibition of the enzyme. Calcium concentration, which inhibited the enzyme 50%, was in the millimolar range for control and in the micromolar range for the obtained enzyme from adrenaline-treated muscles, indicating a different sensitivity to calcium inhibition. We conclude that adrenaline inhibits S-adenosyl-L-homocysteine hydrolase in situ, probably by a calcium-modulated mechanism.
Suárez
J
J
Departamento de Farmacología, Instituto Nacional de Cardiología Ignacio Chávez, México D.F., Mexico.
Chagoya de Sánchez
V
V
D043383:Adenosylhomocysteinase; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004837:Epinephrine / Q000494:pharmacology*; D005452:Fluoresceins; D006168:Guinea Pigs; D006867:Hydrolases / Q000037:antagonists & inhibitors*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects* / Q000201:enzymology; D011433:Propranolol / Q000494:pharmacology; D013268:Stimulation, Chemical
D004791:Enzyme Inhibitors; D005452:Fluoresceins; C110423:dihydrofluorescein; D011433:Propranolol; D006867:Hydrolases; D043383:Adenosylhomocysteinase; D007545:Isoproterenol; D004837:Epinephrine